Pseudorabies is an acute infectious disease of pigs caused by pseudorabies virus (PRV). The outbreak of the disease in pigs can cause miscarriage in pregnancy sows, stillbirths, infertility of male pigs, mass death of newborn piglets, breathing difficulties and growth retardation of feeder pigs, etc. Pseudorabies is one of the major infectious diseases that endanger the global pig industry. It has brought tremendous economic losses to the world pig industry. At present, many European countries have announced the eradication of pseudorabies by vaccination combined with related serological diagnostic techniques. China also effectively controls the epidemic trend of PRV by vaccination. However, in 2011, pseudorabies was prevalent in China even though affected pigs were immunized with pseudorabies vaccine.
The pseudorabies virus is a herpesviridae virus with a circular envelope having a 150-180 nm diameter. The nucleocapsid is mainly composed of proteins encoded by UL19 gene and UL35 gene. There are tegument proteins between the nucleocapsid and the capsid, and at least 14 proteins are derived from the viral genome. The eleven (11) glycoproteins gb, gC, gD, gE, gG, gH, gI, gK, gL, gM and gN that have been identified for their functions. Proteins gB, gD, gH and gL are essential glycoproteins for in vitro replication and infection, and related to PRV nerve conduction. Proteins gC, gE, gG and gM are non-essential glycoprotein for virus replication, wherein gC, gE and gI are related to the PRV in the conduction direction among nerve cells. The virulence of PRV is controlled by a combination of multiple genes. The virulence-related genes are UL10, UL13, UL21, UL23 (TK), UL39/40, UL44, UL50 of UL region, US7, US8. Among them, the deletion of TK or PK leads to a significant decrease of virus virulence.
The gE gene is the encoded product of the US8 gene and is one of the six structural proteins found in the viral envelope. The gE protein is a glycoprotein that promotes cell fusion, promotes the fusion of virus-infected cells with neighboring normal cells, and participates in the spread of the virus among cells and the release of PRV virions. Numerous studies have shown that the absence of gE, although not significantly affecting the LD50 of the virus, can reduce the neurotropic nature of the virus without affecting its immunogenicity.
TK gene is located in the UL23 region, about 900 bp in length, encoding 297 amino acids, and is a major virulence gene of herpes virus. TK is not an essential gene for PRV growth, but plays a key role in the proliferation, replication, latent infection and resurrection of PRV in the host nerve tissue cells and is mainly involved in the replication and latent infection of PRV. The absence of TK can lead to a much reduced virulence of PRV to pigs and ruminants. Studies have shown that immunization of mice with TK-deficient strains can withstand 102-103 fold lethal dose of the parental challenge, and the loss of TK is also a key target of gene-deletion research.
As there is no effective treatment for pseudorabies, immunization with the vaccine becomes a fundamental measure to prevent and control pseudorabies. Now widely used is the vaccine made with the classical pseudorabies virus strains Bartha K61 and BUK. The Bartha K61 strain was repeatedly passed on from Bartha strain in allogeneic cells. BUK is obtained after passage of the attenuated strain of Bucharest strain through 800 generations passages for chicken embryos and chicken embryo fibroblasts, and has certain immunoprotective effects on pregnant sows and piglets. Gene-deleted vaccines are vaccines that use genetic engineering techniques to delete virulence-related genes or fragments of the PRV genome. The advantage of deleting seedlings lies in that the deletion locus is clear and the virulence recovery is not easy to occur, which can be used for distinguishing vaccine strains from wild-type strains. The vaccine is called serological “mark” vaccine and is the key to eradicating pseudorabies. At present, many countries have developed genetically modified strains of classical pseudorabies virus, which play an important role in the prevention, control and eradication of pseudorabies.